4, 7-diamino-2-(substituted)-n-substituted-6-pteridinecarboxamides



United States Patent 3,122,546 4,7-DZAM1NO-2-(SUBSTlTUTED)-N-SUBSTITUTED- 6-PTEPIDHQECARBOXAMIDES Thomas S. Osdene, West Chester, Pa., assignor t0 American Home Products Corporation, New York, N.Y., a

corporation of Delaware No Drawing. Filed Dec. 3, 1962, Ser- No. 241,523 2 Claims. (Cl. 260-251.5}

This invention relates to novel pteridine compounds having significant antiviral properties. More specifically, the invention is concerned with 4,7-diarnino-2-(substituted) -N-substituted-6-pteridinecarboxamides having the formula:

wherein Y and Z may be the same or different and are selected from the group consisting of di-lower alkyl amino radicals in which the alkyl radicals may be the same or dilferent and may have from 1 to 4 carbon atoms in the chain, morpholinyl, pyrrolidinyl, piperazinyl and piperidinyl radicals; R and R may be the same or different and are selected fiom the group consisting of hydrogen and lower alkyl having from 1 to 4 carbon atoms in the chain; A and B may be the same or different and are straight chained or branch alkylene radicals having from 2 to 5 carbon atoms.

The compounds sought to be patented, suitably, are prepared from the corresponding 2-alkylthio-4,7-cliamino- N-(substituted)-6-pteridinecarboxamides, which are disclosed and claimed in co-pending application Serial No. 241,487, filed December 3, 1962. To prepare the compounds of this invention, a 2-alkylthio-4,7-diamino-N-(substituted)-6-pteridinecarboxamide, II, and a primary or secondary amine, III, are refluxed together until the evolution of mercaptan ceases. At this point, the resulting solution is diluted with ethanol and is filtered. The filtrate is concentrated and the residue is repeatedly extracted with ether. Cooling the ether extracts precipitates the product which can be purified by recrystallization from benzene.

The reaction may be represented schematically as follows:

N i N \-CONBZ I HN-AY T Alk-SH NH:

\NAN/ I N CON-BZ Alk-SH wherein the substituents are as above stated.

The following examples represent the best mode of carrying out the invention.

Example 1 A mixture of 3.64 g. of 4,7-diamino-N-(3-diethylaminopropyl)-2-methylmercapto-6-pteridinecarboxamide and 25 0 ml. of S-diethylaminopropylamine were boiled together ice Analysis.-Calculated: C=54.28, H=8.68, N=30. l5. Found: C=54.39, H:8.25, N=29.83.

When applying the above procedure to the starting compounds listed below, there are obtained the corresponding products enumerated below:

Starting Compounds Products 4,7-diamino-N-(Z-(limethyl-amino ethyD-Z-methylmercapto-S- pteridinecarboxamide and 2- morpholinoethylamine. fi-diamino-N-methyl-N- (5-pyrrolidinopentyl)-2-propylmercapto-fi-pteridinecarb oxamide and 2- pyrrolidiuoethylamiue. 4,7-diamino-N butyl-N-(2piperidinoethyl)-2-Iuethylmercapto-6- pteridinccarboxamide and N- butyl-5-piperidinopentylamine. 4,7-diamino-N-(Z-diisopropylaminoethyl)-2-methylrnercapto-B- pteridinecarboxamide and N- methyl-Z-diethylaminoethylamm 4,7diamino-N-(2-morpholinoethylJ-2-methyln1ercapto-6- pteridinecarboxamide and 5-pip- 4,7-diamiuo-N-(Z-dimethyl-aminoethyl) -2-(2-morpholino-ethylamino)-6-pteridinecarboxemide.

4,7-diamino-N-methyl-N-(5-pyrrolidinopentyl)-2-(2 pyrrolidinoethyl-amino)-fi-pteridinecarboxamide.

4,7diamino-Nbutyl-N-(Z-piperidinoethyl)-2-(N-butyl-5-piperidinopentylamino)-6-pteridinecarboxarnide.

4,7-diamino-N-(2-diisopropylaminoethyl)-2 (N-methyl-2-(liethylaminoethylamino)-6-pteridineearboxamide.

4,7-diamiuo-2-(5-piperidinopentylamino)-N-(2-morpholin0ethyl)- 6pteridinecarboxamide.

eridinopentylamine.

The subject compounds are useful in experimental pharmacology and are eliective against SKF Polio and Semliki Forest viral organisms.

The compounds of this invention can be administered in a wide variety of oral or parenteral unit dosage forms singly, or in admixture with other active compounds.

The present invention also includes the process of bringing the compounds thereof into a form suitable for therapeutic administration by associating them with liquid or solid pharmaceutical carriers.

Various changes and modifications of this invention can be made by those skilled in the art to which it relates and to the extent that such variations incorporate the spirit of the invention, they are included in the scope of the claims.

What is claimed is:

1. A compound of the formula:

To ON-IBZ 2. 4,7-diamino-2-(3-diethylaminopropylamino)-N (3- diethylaminopropyl)-6-pteridinecarboxamide.

References Cited in the file of this patent UNITED STATES PATENTS 3,028,387 Weinstock Apr. 3, 1962 

1. A COMPOUND OF THE FORMULA: 